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PHYSIOLOGY AND MAINTENANCE – Vol. III - Heart As An Endocrine Organ - Olli Vuolteenaho
HEART AS AN ENDOCRINE ORGAN
Olli Vuolteenaho
Department of Physiology, Medical Faculty, Biocenter Oulu, University of Oulu,
Finland
Keywords: Natriuretic peptide, heart failure, blood pressure.
Contents
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1. Introduction
2. Adaptation of the Heart to Increased Load
3. Discovery of Cardiac Hormones
4. Physiological Effects of Cardiac Natriuretic Peptides (ANP and BNP)
5. Natriuretic Peptide Receptors
6. Regulation of ANP and BNP
7. Therapeutic Use of Cardiac Hormones
8. Diagnostic Use of Cardiac Hormones
Glossary
Bibliography
Biographical Sketch
Summary
The heart produces two major hormones, A- and B-type natriuretic peptides (ANP and
BNP), which are synthesized and secreted in response to increased workload of the
heart. Their main function is to alleviate cardiac load by decreasing the amount of
extracellular fluid and lowering the blood pressure. They also limit the development of
cardiac hypertrophy and fibrosis, severe consequences of prolonged overloading of the
heart. ANP and especially BNP can be used as drugs in the treatment of acute heart
failure. Finally, increased circulating levels of ANP and BNP or their propeptides can
be used as sensitive markers of impaired cardiac function.
1. Introduction
The heart is a muscular pump which circulates blood to facilitate oxygen and nutrient
supply to the tissues and the disposal of waste. Heart function is essential for life; even a
short cardiac arrest results in the loss of consciousness, and death usually ensues within
minutes.
The vertebrate heart consists of four chambers, the relatively thin-walled right and left
atria and the robust right and left ventricles. The arrangement is, however, not
invariable: in the fish heart, for example, there is only one atrium and one ventricle. The
atria are primer pumps which help the ventricle to fill. The right atrium receives "used"
deoxygenated blood from the veins and pumps it to the right ventricle which in turn
generates the force required to circulate blood through the lungs. The amount of filling
of the ventricle (or the atrial pressure) is called the preload. While passing the lungs the
blood is rejuvenated with oxygen and purified from the carbon dioxide produced by
©Encyclopedia of Life Support Systems (EOLSS)
PHYSIOLOGY AND MAINTENANCE – Vol. III - Heart As An Endocrine Organ - Olli Vuolteenaho
tissue metabolism. The well-oxygenated blood enters the left atrium which pumps it
further to the left ventricle. Finally, the left ventricle has to work hard to be able to
pump blood to the peripheral tissues against the high pressure of the aorta. This arterial
resistance is called the afterload of the ventricle.
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The heart receives both sympathetic and parasympathetic fibers of the autonomous
nervous system. Sympathetic stimulation increase and parasympathetic stimulation
decrease the heart rate and the force of contraction. Hormonal signals from elsewhere in
the body can regulate heart function, too. For example, hormones of the adrenal medulla
stimulate heart electrical activity and contractions. Endothelin, a hormonal substance
produced by the endothelium, the inner cellular lining of the cardiovascular system, is
an inducer of growth and function of vascular smooth muscle and cardiac muscle. On
the other hand, the heart itself appears to produce and secrete hormones which regulate
cardiac function, blood pressure and fluid balance. Thus, both the blood vessels and
heart are capable of regulating the cardiovascular system by means of hormonal signals.
This review will concentrate on the role of the heart as a source of hormones, rather
than as a target of them.
2. Adaptation of the Heart to Increased Load
The heart appears to be a self-regulated pump―pumping into the arteries increases in
proportion to the filling of the heart from the venous side. This has its costs and limits.
The oxygen consumption of the heart is directly related to the amount of blood it
pumps, and also to the pressure against which the ventricles (especially the left) have to
work. Heart failure is a condition in which the heart cannot pump all the blood it
receives without increasing the filling pressure. This is a serious consequence of many
cardiovascular diseases, such as hypertension and valvular defects, but it can also occur
in otherwise healthy people. In fact, during maximal exercise tests, transient "heart
failure" usually marks the limit of performance of a healthy person.
Fortunately, the heart is not helpless in the face of increased demand for pumping
blood. In the short term the stroke volume and heart rate can increase greatly, raising the
cardiac output up to seven times higher compared with the basal resting level.
Prolonged elevated load increases the muscle mass of the heart, i.e. it causes cardiac
hypertrophy. Because mature cardiac muscle cells cannot divide, hypertrophy results
from increased muscle cell size rather than cell number.
Initially this is a beneficial adaptive change which increases the pumping capacity of the
heart. Eventually, however, it leads to reduced cardiac function and dire consequences,
especially if the supply of oxygen or nutrients to the cardiac muscle cells is
compromised. Increased muscle cell mass raises the oxygen consumption and therefore
predisposes the hypertrophic heart to ischemia, lack of oxygen. It also makes the heart
more susceptible to arrhythmias. Moreover, the amount of cardiac connective tissue
increases hand in hand with increased muscle cell mass causing cardiac fibrosis. This
makes the heart stiffer and therefore more difficult to fill, a condition known as diastolic
heart failure. In the long run a perhaps more constructive response of the heart to
increased load is to send hormonal signals which cause physiological reactions that
reduce cardiac load.
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PHYSIOLOGY AND MAINTENANCE – Vol. III - Heart As An Endocrine Organ - Olli Vuolteenaho
3. Discovery of Cardiac Hormones
In addition to being a pump the heart has also been found to have an endocrine function,
i.e. it sends hormonal signals which cause changes in the function of other organs and
cells of the body. While many hormones which are also produced elsewhere in the body
can be found in the heart, natriuretic peptides appear to be the only ones that are
characteristically cardiac hormones.
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In retrospect it can be seen that electron microscopical studies had hinted for a
secretory, perhaps endocrine, role for the heart as early as the 1950s and 1960s. The
Canadian scientist Adolfo de Bold, however, is the real discoverer of the endocrine
heart. He found in the early 1980s that injection into rats of acid extracts of cardiac atria
caused briskly increased output of water and sodium to the urine, i.e. diuresis and
natriuresis, and lowered the blood pressure. He and his compatriot Geoff Flynn rapidly
isolated and characterized the novel 28-amino acid peptide hormone responsible for the
activity. They initially named it cardionatrin, but nowadays it is called atrial natriuretic
peptide or A-type natriuretic peptide (ANP). A few years later, two related peptides, Btype natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) were isolated. BNP
is a 32-amino acid peptide in humans, and it is mainly produced by the heart ventricles.
The 22-amino acid CNP is not, however, a cardiac hormone in mammals. Rather, it is
distributed in low concentrations in many tissues. Similar peptide hormones can be
found in all vertebrates, and functional studies have shown that they serve important
well-conserved regulatory functions. The structures of the genes encoding the
natriuretic peptides are known. On the basis of the structures it seems clear that they
belong to the same peptide family which has risen by repeated gene duplications. Of the
mammalian hormones, CNP is structurally the most conserved and appears to be the
most ancient, perhaps representing the parent peptide. ANP is also highly conserved in
different species, whereas the structure of BNP varies to a surprising degree. The
structure of BNP, for example, sometimes bears more resemblance to ANP of the same
species than to BNPs of other species (see Figure 1).
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Bibliography
Ala-Kopsala M., Magga J., Peuhkurinen K., Leipälä J., Ruskoaho H., Leppäluoto J. and Vuolteenaho O.
(2004). Molecular heterogeneity has a major impact on the measurement of circulating N-terminal
fragments of A- and B-type natriuretic peptides. Clinical Chemistry 50(9). In press. [Biochemical analysis
of the heart disorders is possible by using blood samples.]
de Bold A.J. (1987). On the shoulders of giants: the discovery of atrial natriuretic factor. Canadian
Journal of Physiology and Pharmacology 65(10) 2007-2012. [An overview of the steps taken to reveal
heart as an endocrine organ.]
©Encyclopedia of Life Support Systems (EOLSS)
PHYSIOLOGY AND MAINTENANCE – Vol. III - Heart As An Endocrine Organ - Olli Vuolteenaho
Ganong W.F. (2003). Review of Medical Physiology. 21st Edition. Lange Medical Books/McGraw-Hill.
[A comprehensive overview of the circulatory system and other body functions.]
Mäkikallio K., Vuolteenaho O., Jouppila P. and Räsänen J. (2002). Ultrasonographic and biochemical
markers of human fetal cardiac dysfunction in placental insufficiency. Circulation 105, 2058-2063. [Fetal
cardiac health can be studied with biophysical and also biochemical methods during pregnancy.]
Matsuo H. (2001). Discovery of a natriuretic peptide family and their clinical application. Canadian
Journal of Physiology and Pharmacology 79, 736-740. [The title indicates the content.]
Richards A.M. (2004). The natriuretic peptides in heart failure. Basic Research in Cardiology 99, 94-100.
[The endocrine function of the heart reveals the pathophysiological state of the circulatory system.]
Ruskoaho H. (2003). Cardiac hormones as diagnostic tools in heart failure. Endocrine Reviews 24, 341356. [Biochemical analyses complement biophysical measurements like electrocardiography.]
Wilkins M.R., Redondo J. and Brown L.A. (1997). The natriuretic-peptide family. Lancet 349,1307-1310.
[A short overview of clinical aspects of cardiac hormones.]
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Biographical Sketch
Olli Vuolteenaho born in 1958. He is a Professor of Physiology and chairman, Department of
Physiology, University of Oulu, Finland.
He has many publications on neuroendocrinology, molecular biology, peptide biology and cardiovascular
physiology.
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